Search

Abstract Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson’s Disease (PD) are in early phases of clinical testing. Involving patients’ preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects. Demonstrating a non-gaussian distribution, risk willingness varied markedly within, and between groups. MSA patients accepted a median 1% risk [interquartile range: 0.001–25%] of sudden death for a 99% [interquartile range: 99.999–75%] chance of cure, while PD patients reported a median 0.055% risk [interquartile range: 0.001–5%]. Contrary to our hypothesis, a considerable proportion of MSA patients, despite their substantially impaired quality of life, were not willing to accept increased therapy-associated risks. Satisfaction with life situation, emotional, and nonmotor disease burden were associated with MSA patients’ risk willingness in contrast to PD patients, for whom age, and disease duration were associated factors. An individual approach towards MSA and PD patients is crucial as direct inference from disease (stage) to therapy-associated risk willingness is not feasible. Such studies may be considered by regulatory agencies in their approval processes assisting with the weighting of safety aspects in a patient-centric manner. A systematic quantitative assessment of patients’ risk willingness and associated features may assist physicians in conducting individual consultations with patients who have MSA or PD by facilitating communication of risks and benefits of a treatment option.

Abstract Background Post-stroke dysphagia (PSD) is common and can lead to serious complications. Pharyngeal sensory impairment is assumed to contribute to PSD. The aim of this study was to investigate the relationship between PSD and pharyngeal hypesthesia and to compare different assessment methods for pharyngeal sensation. Methods In this prospective observational study, fifty-seven stroke patients were examined in the acute stage of the disease using Flexible Endoscopic Evaluation of Swallowing (FEES). The Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and impaired secretion management according to the Murray-Secretion Scale were determined, as well as premature bolus spillage, pharyngeal residue and delayed or absent swallowing reflex. A multimodal sensory assessment was performed, including touch-technique and a previously established FEES-based swallowing provocation test with different volumes of liquid to determine the latency of swallowing response (FEES-LSR-Test). Predictors of FEDSS, Murray-Secretion Scale, premature bolus spillage, pharyngeal residue, and delayed or absent swallowing reflex were examined with ordinal logistic regression analyses. Results Sensory impairment using the touch-technique and the FEES-LSR-Test were independent predictors of higher FEDSS, Murray-Secretion Scale, and delayed or absent swallowing reflex. Decreased sensitivity according to the touch-technique correlated with the FEES-LSR-Test at 0.3 ml and 0.4 ml, but not at 0.2 ml and 0.5 ml trigger volumes. Conclusions Pharyngeal hypesthesia is a crucial factor in the development of PSD, leading to impaired secretion management and delayed or absent swallowing reflex. It can be investigated using both the touch-technique and the FEES-LSR-Test. In the latter procedure, trigger volumes of 0.4 ml are particularly suitable.

Abstract Dysphagia is common in Parkinson’s disease (PD) and is assumed to complicate medication intake. This study comprehensively investigates dysphagia for medication and its association with motor complications in PD. Based on a retrospective analysis, a two-dimensional and graduated classification of dysphagia for medication was introduced differentiating swallowing efficiency and swallowing safety. In a subsequent prospective study, sixty-six PD patients underwent flexible endoscopic evaluation of swallowing, which included the swallowing of 2 tablets and capsules of different sizes. Dysphagia for medication was present in nearly 70% of PD patients and predicted motor complications according to the MDS-UPDRS-part-IV in a linear regression model. Capsules tended to be swallowed more efficiently compared to tablets, irrespective of size. A score of ≥1 on the swallow-related-MDS-UPDRS-items can be considered an optimal cut-off to predict dysphagia for medication. Swallowing impairment for oral medication may predispose to motor complications.